ABSTRACT: Objective: Alpelisib-induced diabetic ketoacidosis (DKA) is a rare, but life-threatening, adverse event. There have been only 2 reported cases in the literature. We describe such a case, with emphasis on the importance of screening and achieving adequate glycemic control prior to and after initiation of therapy. Methods: A 49-year-old woman, known to have advanced breast cancer, presented with a 3-day history of nausea, vomiting, and diffuse abdominal pain. She had started alpelisib at 300 mg/day 2 months prior to presentation, after failing other options. She was diagnosed with DKA using her clinical and laboratory features, leading to treatment with hydration and intravenous insulin therapy. Results: Laboratory data showed high anion gap metabolic acidosis, hyperglycemia, and ketonemia with negative GAD-65 antibodies, leading to the diagnosis of alpelisib-associated DKA. Alpelisib was held, and she was treated with intravenous insulin and hydration. When DKA and hyperglycemia resolved, alpelisib was resumed at a lower dose (200 mg/day) and her blood glucose was managed using a regimen combining insulin and metformin. Conclusion: Phosphatidylinositol-3 kinase signaling is important for the metabolic actions of insulin, and alpelisib has been associated with severe hyperglycemia. Metformin is the first-line treatment, however when DKA is the presenting syndrome, insulin needs to be considered. Blood glucose and hemoglobin A1c should be checked prior to treatment initiation and monitored closely after drug initiation. DKA, albeit rare, must be considered in an acutely ill, alpelisib-treated patients presenting with metabolic acidosis, and if drug discontinuation is not an option, insulin treatment may be required to control glycemia. Abbreviations: DKA diabetic ketoacidosis HbA1c hemoglobin A1c PI3K phosphatidylinositol-3 kinase
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